Amine oxidases in bovine serum generate products that are cytotoxic and mutagenic to cultured human and murine cells. Short-term toxicity of these byproducts is seen as a lack of survival of hematopoietic progenitor cells, associated with low cloning efficiencies. Long-term toxicity is seen as in vitro evolution of primary cultures of mouse embryo cells, leading to "immortalization." Therefore, during the Phase I Grant, we studied the feasibility of purifying the amine oxidases in bovine serum, in order to generate amine oxidase-depleted bovine serum. The Phase II application will involve generating amine oxidase-free bovine serum by elimination of enzyme activity. This serum will be tested in various short-term and long-term blood cell cultures.